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Current Cancer Drug Targets

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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General Research Article

TROP2 Down-regulated DSG2 to Promote Gastric Cancer Cell Invasion and Migration by EGFR/AKT and DSG2/PG/β-Catenin Pathways

Author(s): Tingting Yang, Lizhou Jia, Susu Bian, Xinxia Chang, Qian Zhang, Qi Tang, Jing Zhu, Zhiping Yang* and Zhenqing Feng*

Volume 22, Issue 8, 2022

Published on: 09 June, 2022

Page: [691 - 702] Pages: 12

DOI: 10.2174/1568009622666220407111013

Price: $65

Abstract

Background: Gastric cancer (GC) is the fourth most commonly found cancer and the second- highest cause of cancer-related death worldwide. TROP2 overexpression is closely related to many cancers, including gastrointestinal tumors. DSG2 is an important protein in cell adhesion, and its loss affects cell migration.

Aims and Objective: This study aimed to explore the specific mechanism of TROP2 in promoting gastric cancer and provide a basis for the prevention and treatment of gastric cancer.

Method: DSG2 was identified as an interacting protein of TROP2 in GC cells by coimmunoprecipitation and mass spectrometry. The regulated behavior of TROP2 on DSG2 expression was investigated with TROP2 over-expressure or knockdown. Cell-cell adhesion capacity mediated by DSG2 was evaluated by adhesion-related assays. Electron microscope observation was made for accessing GC tumor desmosome assembly. Proteins in EGFR/AKT and DSG2/PG/β-catenin pathways were evaluated by western blotting.

Result: This study suggests that abundant expression of TROP2 in GC cells lessened DSG2 levels as well as desmosome adhesion, increased cell invasion and migration, and promoted malignant progression through EGFR/AKT and DSG2/PG/β-catenin pathways.

Conclusion: TROP2 promotes cell invasion and migration in gastric cancer by decreasing DSG2 expression through EGFR/AKT and DSG2/PG/β-catenin pathways.

Keywords: TROP2, DSG2, gastric cancer, desmosome, adhesion, interacting protein.

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